不同抗高血压药物对自发性高血压大鼠痛阈的影响

The effects of different antihypertensive drugs on pain threshold in spontaneously hypertensive rats

目的观察不同抗高血压药物对自发性高血压大鼠(SHR)痛阈的影响,探讨其与血管紧张素Ⅱ(AngⅡ)的关系。方法 12周龄雄性SHR 40只随机分为卡托普利[100 mg/(kg·d)]、氯沙坦[50 mg/(kg·d)]、普萘洛尔[40mg/(kg·d)]、非洛地平组[10mg/(kg·d)]和SHR对照组,并选取对应周龄雄性Wistar-Kyoto(WKY)大鼠作为正常血压对照组,每组8只,灌胃8周。采用无创尾袖法测量大鼠尾动脉收缩压。测量给药前、给药4和8周时大鼠的机械痛阈和热痛阈。应用酶联免疫吸附试验(ELISA)测定大鼠血浆及脊髓组织AngⅡ。结果卡托普利、氯沙坦、普萘洛尔、非洛地平治疗4和8周后,收缩压明显低于SHR对照组[4周:(178±9)、(168±10)、(177±11)、(172±7)比(201±10)mm Hg;8周:(177±9)、(166±10)、(176±7)、(172±8)比(200±11)mm Hg;均P<0.01]。SHR治疗前机械痛阈高于WKY,热痛阈低于WKY(P<0.01)。卡托普利组和氯沙坦组治疗4和8周末,机械痛阈和热痛阈较给药前明显升高(P<0.01);与SHR对照组比较,机械痛阈和热痛阈有不同程度升高(P<0.01或P<0.05)。卡托普利组和非洛地平组的血浆AngⅡ较SHR对照组减低(P<0.05),氯沙坦组血浆AngⅡ明显高于其他组(P<0.01);卡托普利组的脊髓AngⅡ较其他各组显著降低(P<0.05)。相关分析表明,痛阈改变与脊髓AngⅡ相关(P<0.01)。结论卡托普利和氯沙坦治疗高血压可增高SHR痛阈,其原因可能与脊髓水平AngⅡ下降或脊髓AngⅡ痛敏作用被阻滞有关。

Objective To investigate the effects of different antihypertensive drugs on pain threshold in spontaneously hypertensive rats （SHR）, and to explore their relationship with angiotensin II （Ang II ）. Methods Forty 12-week-old male SHR were randomly assigned to five groups： captopril treated group [100 mg/（kg · d）], losartan treated group 1-50 mg/（kg · d）], propranolol treated group 1-40 mg/（kg · d）], felodipine treated group [10 mg/（kg · d}] and untreated control group. The rats in the treated groups were given antihypertensive drugs by gavage for 8 weeks, and the SHR control group was given normal saline by gavage for 8 weeks. And 12-week-old male Wistar-Kyoto （WKY） rats were taken as the normal blood pressure control group. There were 8 rats in each group. Systolic blood pressure was measured by tail-cuff method. The mechanical withdrawal threshold （MWT） and thermal withdrawl latency （TWL） were detected before treatment, at the end of 4th week and 8th week of treatment, respectively. The concentrations of Ang II in the plasma and spinal cord were determined by enzyme linked immunosorbent assay （ELISA）. Results At the end of 4th week and 8th week, compared with the SHR control group, systolic blood pressure in the captopril treated group, losartan treated group, propranolol treated group and （elodip ine treated group was significantly decreased1-4th week： （ 178 ±9 ） , （ 168 ± 10 ） , （ 177 ± 11 ） , （ 172 ± 7 ） vs （ 201± 10） mmHg; 8th week： （177±9）, （166±10）, （176±7）, （172±8） vs （200±11） mmHg;all P〈0.01]. Compared with WKY rats, MWT was higher and TWL was lower in SHR before treatment （P〈0.01）. At the end of 4th week and 8th week, MWT and TWL were significantly higher in the captopril group and losartan group than those before treatment （all P〈0.01） ; and compared with the SHR control group, MWT and TWL were increased in the captopril group and losartan group （P〈0.01 or P〈0.05）. The plasma concentration of Ang II in the captopril group and felodipine group was lower than that in the SHR control group （P〈0.05）. The plasma concentration of Ang II in the losartan group was obviously higher than that in other groups （P〈0.01）. Spinal concentration of Ang II in the captopril group was obviously lower than that in other groups （P〈0.01）. Correlation analysis showed that pain threshold was related to spinal concentration of Ang II （P〈0.05）. Conclusion Antihypertensive treatment with captopril or losartan couid increase pain threshold in SHR, which may be related to the decrease of Ang II concentration or blocked hyperalgesia effect of Ang II in the spinal cord.